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Carotenoids have antioxidant properties, and the accumulation of advanced glycation end products (AGEs) is associated with reactive oxygen species production; they have attracted attention as factors predictive of the onset and progression in glaucoma. Fingertip measurement is applicable for carotenoids and AGEs due to its noninvasiveness and simplicity. The study included 663 eyes of 663 Japanese subjects (357 males, 306 females). The mean age was 69.9 years with a standard deviation of 11.0. The study population comprised participants with primary open-angle glaucoma (PG) (n = 358), exfoliation glaucoma (EG) (n = 168), and controls (n = 137). Multivariate models suggested that lower skin carotenoid (SC) levels were associated with male gender (standard β = −0.14), AGE scores (−0.24), and a history of intraocular surgery (−0.22). Higher SC levels were associated with higher vegetable intake scores (0.21 for score 3) and diabetes (0.10). However, no association was seen between SCs and glaucoma type. AGEs levels were negatively associated with carotenoid scores (−0.25), PG (−0.15), and smoking habits (−0.26) and positively correlated with EG (0.14). SCs and AGEs were negatively correlated in the single regression analysis (r = −0.20, p < 0.0001). In conclusion, higher levels of AGEs may be candidates for systemic biomarkers of glaucoma associated with the exfoliation syndrome. SC levels can reflect self-reported daily vegetable intake.

Oxidative stress is thought to play a significant role in the development of glaucoma. However, the association between systemic and local oxidative stresses in different types of glaucoma has not been assessed fully. The current study compared the redox status in the aqueous humor (AH) and blood samples among eyes with primary open-angle glaucoma (POAG), exfoliation glaucoma (EXG), and non-glaucomatous controls to evaluate the relationship among systemic redox status, intraocular oxidative stress, and clinical backgrounds. AH and blood samples were obtained from 45 eyes of 45 Japanese subjects (15 POAG, 15 EXG, and 15 control eyes). The serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolites (dROM), biologic antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer. The activities of cytosolic and mitochondrial forms of the superoxide dismutase (SOD) isoforms, i.e., SOD1 and SOD2, respectively, in AH and serum were measured using a multiplex bead immunoassay. In AH, SOD1 in subjects with EXG and SOD2 in those with POAG and EXG were significantly higher than in control eyes. In serum, compared to control subjects, BAP in subjects with POAG and EXG was significantly lower; SOD1 in those with EXG and SOD2 in those with POAG and EXG were significantly higher. dROM and SH did not differ significantly among the groups. The BAP values were correlated negatively with the SOD1 concentrations in AH and serum, SOD2 in the AH, intraocular pressure, and number of antiglaucoma medications. In conclusion, lower systemic antioxidant capacity accompanies up-regulation of higher local antioxidant enzymes, suggesting increased oxidative stress in eyes with OAG, especially in EXG. Determination of the systemic BAP values may help predict the redox status in AH.

Advanced glycation end products (AGEs) and carotenoids, the major prooxidants and antioxidants in vivo, respectively, are thought to be associated with diabetes mellitus (DM). To estimate AGEs and carotenoid levels simultaneously in patients with DM, we used noninvasive fingertip skin sensors. The study population included 249 eyes of 249 Japanese subjects (130 men, 119 women; mean age ± standard deviation, 69.9 ± 12.0 years). Ninety-three patients had DM, which included diabetic retinopathy (DR) (n = 44) and no DR (NDR) (n = 49), and 156 controls. Compared to the controls (0.44 ± 0.07 arbitrary unit (A.U.)), the AGEs scores were significantly higher in DM (0.47 ± 0.09, p = 0.029) and DR (0.49 ± 0.08, p = 0.0006) patients; no difference was seen between NDR (0.45 ± 0.09, p = 0.83) and controls. Multivariate analyses indicated that a higher AGEs level is a risk factor for DR (r = 0.030, p = 0.0025). However, the carotenoid scores did not differ in any comparisons between the controls (327.7 ± 137.0 O.D.) and patients with DM (324.7 ± 126.4, p = 0.86), NDR (320.4 ± 123.6, p = 0.93), or DR (329.4 ± 130.8, p = 0.93). The carotenoid scores correlated negatively with the AGEs scores (r = −0.21, p = 0.0007), and reflected the Veggie intake score (p < 0.0001). In patients with DM, estimations of AGEs and carotenoid levels using skin sensors can be useful for assessing their risk of DR and vegetable intake, respectively.

Background To assess the efficacy of toric intraocular lenses (IOLs) in combined cataract and minimally invasive glaucoma surgery (MIGS), visual and refractive outcomes were compared between eyes implanted with non-toric and toric IOLs during iStent triple procedures. Methods In this retrospective study, open angle glaucoma eyes with preexisting corneal astigmatism of -1.5 diopter (D) or more and implanted with non-toric (n = 9) or toric (n = 9) IOLs were included. The main outcome measures were the intergroup difference in the uncorrected visual acuity (UCVA) and refractive astigmatism at 3 months postoperatively. Results Preoperatively, the logarithm of the minimum angle of resolution (logMAR) UCVAs and refractive astigmatism were equivalent between the groups. Postoperatively, the logMAR UCVA (non-toric, 0.45 ± 0.31; toric, 0.14 ± 0.15; P  = 0.021) was significantly better and the refractive astigmatism (non-toric, -2.03 ± 0.63 D; toric, -0.67 ± 0.53 D; P  = 0.0014) significantly less in the toric group. The toric group had postoperative improvements in the logMAR UCVA (-0.21, P  = 0.020) and refractive astigmatism (+ 1.72 D, P  = 0.0039). Vector analyses showed the postoperative centroid magnitude and confidence eclipses of refractive astigmatism was less in the toric group (0.47 D at 173°±0.73D) than the non-toric group (1.10 D at 2°±1.91D). Postoperatively, 78% of eyes in the toric group had 1.0 D or less refractive astigmatism compared with 11% in the non-toric group. Surgically induced astigmatism (non-toric, 0.18 D at 65°; toric, 0.29 D at 137°) did not differ between groups. Conclusion Use of toric IOLs is a reasonable option for better visual outcomes when the combined cataract and iStent surgery is performed in glaucomatous eyes with corneal astigmatism.

The aim of this study is to compare the surgical efficacy and safety between microhook ab-interno trabeculotomy (µLOT) and iStent trabecular micro-bypass stent implantation when both were combined with cataract surgery in both eyes of patients. Sixty-four glaucomatous eyes (32 participants; mean age, 75.9 ± 7.6 years; 15 men, 17 women) were included retrospectively. Intraocular pressure (IOP), number of antiglaucoma medications, best-corrected visual acuity (BCVA), anterior chamber flare (ACF) and corneal endothelial cell density (CECD) were evaluated preoperatively, as well as 2, 3, 6, and 12 months postoperatively. Surgical complications and interventions were compared between the procedures. The preoperative IOP and medications with µLOT (18.8 ± 5.7 mmHg and 3.0 ± 1.2, respectively) were higher than with the iStent (15.5 ± 3.4 mmHg and 2.7 ± 1.2, respectively) (p = 0.0001 and p = 0.0437, respectively). At 12 months, the µLOT values (12.6 ± 2.3 mmHg and 2.3 ± 0.9, respectively) were identical to iStent (12.8 ± 2.5 mmHg and 2.3 ± 0.9, respectively) (p = 0.0934 and p = 0.3251, respectively). At 12 months, the IOP decreased more with µLOT (6.2 mmHg, 29.5%) than iStent (2.7 mmHg, 15.6%) (p = 0.0003). The decrease in medications was greater with µLOT (0.7) than iStent (0.4) (p = 0.0437). Survival rate of IOP control ≤15 mmHg and IOP reduction ≥20% was significantly higher after µLOT (40.6% at 12 months) than iStent (18.8%) (p = 0.0277). The frequency of layered hyphema was significantly greater with µLOT (8 eyes, 25%) than iStent (0 eyes, 0%) (p = 0.0048). The increase in the ACF at 2 weeks postoperatively was significantly greater with µLOT than iStent (p = 0.0156), while changes in the BCVA and CECD were identical between groups. The fellow-eye comparison showed that the IOP reduction was greater with µLOT than iStent when combined with cataract surgery.

The retinal vessel narrowing may be implicated in the pathogenesis of glaucoma; however, the association between systemic oxidative stress and retinal vessel diameter remains largely unknown. We examined the relationship between serum oxidative stress markers and retinal vessel diameters in eyes with primary open-angle glaucoma (POAG) and cataract, using central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE). We included 66 eyes of 66 patients with POAG (37 men, 29 women; 65.4 ± 11.7 years) and 20 eyes of 20 patients with cataract (7 men, 13 women; 69.4 ± 9.0 years) as the controls. The CRAE (p < 0.0001), CRVE (p < 0.0001), and serum biological antioxidant potential (BAP) (p = 0.0419) were significantly lower in the POAG group compared to the controls. The BAP showed significant correlation both with CRAE (ρ = 0.2148, p = 0.0471) and systolic blood pressure (ρ = −0.2431, p = 0.0241), while neither Diacron reactive oxygen metabolites nor sulfhydryl test correlated with them. The multivariate analyses indicated that age, best corrected visual acuity, and BAP were independent factors for CRAE or CRVE. The present study suggested that lower systemic antioxidant capacity was significantly associated with the intraocular pressure-independent vascular narrowing in POAG patients. This study provided a novel insight into the pathophysiology of glaucoma and highlighted the clinical impact on systemic antioxidant treatment for patients with glaucoma.

Advanced glycation end products (AGEs) are thought to play important roles in the pathogenesis of diabetic microangiopathy, particularly in the progression of diabetic retinopathy (DR). We assessed the levels of skin autofluorescence (sAF) to assess the association between AGEs and DR stages. A total of 394 eyes of 394 Japanese subjects (172 men, 222 women; mean age ± standard deviation [SD], 68.4 ± 13.7 years) comprised the study population, i.e., subjects with diabetes mellitus (DM) (n = 229) and non-diabetic controls (n = 165). The patients with DM were divided into those without DR (NDR, n = 101) and DR (n = 128). DR included simple (SDR, n = 36), pre-proliferative (PPDR, n = 25), and PDR (n = 67). Compared to controls (0.52 ± 0.12), the AGE scores were significantly higher in patients with DM (0.59 ± 0.17, p < 0.0001), NDR (0.58 ± 0.16, p = 0.0012), and DR (0.60 ± 0.18, p < 0.0001). The proportion of patients with PDR was significantly higher in the highest quartile of AGE scores than the other quartiles (p < 0.0001). Compared to those without PDR (SDR and PPDR), those with PDR were younger (p = 0.0006), more were pseudophakic (p < 0.0001), had worse visual acuity (VA) (p < 0.0001), had higher intraocular pressure (IOP) (p < 0.0001), and had higher AGE scores (p = 0.0016). Multivariate models also suggested that younger age, male gender, pseudophakia, worse VA, higher IOP, and higher AGE scores were risk factors for PDR. The results suggested that AGE scores were higher in patients with DM and were independently associated with progression of DR. In addition, more PDR was seen in the highest quartile of AGE scores. This study highlights the clinical use of the AGE score as a non-invasive, reliable marker to identity patients at risk of sight-threatening DR.

The antioxidant and anti-inflammatory effects of carotenoid have been determined to aid in the prevention of a wide range of oxidative disorders, arteriosclerosis, obesity, and various types of cancers. In order to keep high carotenoid levels in the body, much of the vegetable and fruit (V/F) intake is mandatory. However, the actual intake of V/F is not enough in many countries. The aim of this study was to assess whether brief dietary education using the Veggie Meter (VM) that could measure skin carotenoid (SC) levels could induce the increase in carotenoid levels via V/F intake. Two hundred and sixty-one elementary and junior high school students (ages 7–14 years old) received brief educational session and SC evaluation by VM, and the changes in SC levels were examined after 6 months. The baseline VM scores ranged from 131 to 825, and the average significantly increased from 400.0 ± 124.7 (standard deviation) to 447.4 ± 140.4 at Month 6 (p < 0.0001). The percentage of increase at month 6 was negatively correlated with the baseline values (r = −0.36, p < 0.0001). This finding implies that subjects who became aware of their inferiority tended to make a significant effort to change their behavior. The multivariate logistic regression analysis demonstrated that subjects taking much of green and yellow vegetables, drinking vegetable/tomato juice, and eating any fruit had higher VM scores than the average value. In conclusion, the educational approach using VM was supposed to be an effective method of raising awareness of the V/F shortage and increasing V/F intake that could indue the increase in SC levels.

We have been using our in-house scoring system of hyphemas, i.e., Shimane University RLC postoperative hyphema scoring system (SU-RLC), which we designed to classify postoperative hyphema. SU-RLC classifies the severities of hyphemas based on three factors, i.e., red blood cells (RBCs) (R) 0–3, layer formation (L) 0–3, and clot (C) 0–1, by slit-lamp observation. To test the clinical usefulness of the SU-RLC for quantifying the postoperative hyphema severity, the SU-RLC scores were compared between eyes that underwent different minimally invasive glaucoma surgery (MIGS) procedures, i.e., Tanito microhook ab interno trabeculotomy and cataract extraction (TMH-CE) (n = 64 eyes of 64 subjects; mean age ± standard deviation, 72.4 ± 8.1 years) and iStent-CE (n = 21 eyes of 21 subjects; 76.1 ± 10.6 years). Compared to the iStent-CE, higher hyphema scores with the TMH-CE were found for the R scores on postoperative days 1, 2, and 3; for the L score on postoperative day 1; and for the C score on postoperative day 2. The sums of the R, L, and C scores (RLC) on postoperative day 1 were 3.2 ± 1.1 with the TMH-CE and 1.1 ± 1.3 with the iStent-CE; the scores reached almost 0 by 2 weeks in both groups. Significant differences in the RLC scores between the surgical groups were found on postoperative days 1, 2, and 3. Multivariate analyses showed that the TMH-CE rather than iStent-CE was associated with higher R, C, and RLC scores; anticoagulant/antiplatelet use was associated with higher R score; and myopia was associated with a higher C score. In the TMH-CE group, myopia was associated with a higher C score. In the iStent-CE group, anticoagulant/antiplatelet use was associated with higher R and RLC scores; and higher postoperative 1-day intraocular pressure was associated with a higher C score. The SU-RLC successfully detected the difference in hyphema severity between different MIGS procedures; thus, we concluded that our classification system may be feasible to evaluate hyphemas after glaucoma surgery.

A 72-year-old Japanese woman presented to our hospital with decreased vision. At the initial visit, her best-corrected visual acuity (BCVA) and intraocular pressure (IOP) in her right eye (OD) were 0.02 and 36 mm Hg, respectively. By slit lamp examination, rubeosis iridis was observed on the iris surface. With higher magnification observation, movement of clustered RBCs were clearly observed; the blood drained into episcleral vessels that were connected with the main trunk of rubeosis iridis. She was diagnosed with the neovascular glaucoma secondary to central retinal vein occlusion OD. She underwent panretinal photocoagulation, intravitreal injection of aflibercept, and Ahmed Glaucoma Valve implantation. At 2 weeks postoperatively, the BCVA and IOP OD were 0.2 and 7 mm Hg, respectively; rubeosis iridis was partially regressed and movement of RBCs was not observed. Acquisition of directional flow by the connection of the main trunk of neovessels with the episcleral vessels and reduction of flow speed by the high IOP could explain the reason for visible blood flow in our case.